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Drug Metabolism and Bioanalysis Letters

Author(s): Shrutika Sakpal*, Shanker Lal Kothari and Virupaksha Bastikar

DOI: 10.2174/1872312815666220225155728

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Characterization of Human-malarial Parasite Species based on DHFR and GST Targets Resulting in Changes in Anti-malarial Drug Binding Conformations

Page: [22 - 37] Pages: 16

  • * (Excluding Mailing and Handling)

Abstract

Background: In this study, we focused primarily on three anti-malarial drugs, namely chloroquine, mefloquine, and proguanil, and these were tested against two malarial targets DHFR and GST. The species Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, Plasmodium vivax were used for the study.

Objective: The purpose of this study was to determine the sequence and structural similarity of the proteins DHFR and GST among four Plasmodium species as well as to discover the in silico interactions with the aforementioned drug candidates.

Methods: Bioinformatics databases, such as PDB, UniProt, DrugBank, PubChem, and tools, and software like Phyre 2.0, Clustal O (1.2.4), AutoDock 4, AutoDock Vina, and Discovery Studio Visualizer were used to determine the evolutionary significance of the Plasmodium species.

Result: The variations showed a difference in the binding patterns of drugs with our target proteins. Our finding reveals the Plasmodium spp divergence or convergence as well as the structural and sequential similarity or dissimilarity features.

Conclusion: Our result suggests that due to the deviation in the sequences and structures, variations in protein-drug binding patterns have emerged.

Keywords: Antimalarial drugs, structural biology, phylogenetic analysis, molecular docking, DHFR, GST.

Graphical Abstract

[1]
Tse, E.G.; Korsik, M.; Todd, M.H. The past, present and future of anti-malarial medicines. Malar. J., 2019, 18(1), 93.
[http://dx.doi.org/10.1186/s12936-019-2724-z] [PMID: 30902052]
[2]
Ondeto, B.M.; Nyundo, C.; Kamau, L.; Muriu, S.M.; Mwangangi, J.M.; Njagi, K.; Mathenge, E.M.; Ochanda, H.; Mbogo, C.M. Current status of insecticide resistance among malaria vectors in Kenya. Parasit. Vectors, 2017, 10(1), 429.
[http://dx.doi.org/10.1186/s13071-017-2361-8] [PMID: 28927428]
[3]
Cui, L.; Mharakurwa, S.; Ndiaye, D.; Rathod, P.K.; Rosenthal, P.J. Antimalarial drug resistance: Literature review and activities and find-ings of the ICEMR network. Am. J. Trop. Med. Hyg., 2015, 93(3)(Suppl.), 57-68.
[http://dx.doi.org/10.4269/ajtmh.15-0007] [PMID: 26259943]
[4]
Ayala, F.J. Phylogeny of the malarial genus Plasmodium, derived from rRNA gene sequences. Proc. Natl. Acad. Sci. USA, 1994, 91(24), 11373-11377.
[5]
Carpenter, C.C.J.; Pearson, G.W.; Mitchell, V.S.; Oaks, S.C., Jr Malaria: Obstacles and opportunities; National Academies Press: Washington D.C., USA, 1991.
[6]
Oaks, S.C., Jr; Mitchell, V.S.; Pearson, G.W.; Carpenter, C.C.J. Parasite Biology.Malaria: Obstacles and Opportunities; National Academies Press: Washington, D.C., 1991.
[7]
Coulson, R.M.R.; Hall, N.; Ouzounis, C.A. Comparative genomics of transcriptional control in the human malaria parasite Plasmodium falciparum. Genome Res., 2004, 14(8), 1548-1554.
[http://dx.doi.org/10.1101/gr.2218604] [PMID: 15256513]
[8]
Anderson, A.C. Targeting DHFR in parasitic protozoa. Drug Discov. Today, 2005, 10(2), 121-128.
[http://dx.doi.org/10.1016/S1359-6446(04)03308-2] [PMID: 15718161]
[9]
Manuscript, A.; Parasite, M.; Host, H. Concubitu prohibere Vago: Sex and the Idiot Girl, 1846-1913. NIH Public Access, 2013, 296(5567), 81-108.
[http://dx.doi.org/10.1126/science.1068274.Divergent]
[10]
Westling, J.; Yowell, C.A.; Majer, P.; Erickson, J.W.; Dame, J.B.; Dunn, B.M. Plasmodium falciparum, P. vivax, and P. malariae: A com-parison of the active site properties of plasmepsins cloned and expressed from three different species of the malaria parasite. Exp. Parasitol., 1997, 87(3), 185-193.
[http://dx.doi.org/10.1006/expr.1997.4225] [PMID: 9371083]
[11]
Sohail, M.; Kumar, R.; Kaul, A.; Arif, E.; Kumar, S.; Adak, T. Polymorphism in glutathione S-transferase P1 is associated with suscepti-bility to Plasmodium vivax malaria compared to P. falciparum and upregulates the GST level during malarial infection. Free Radic. Biol. Med., 2010, 49(11), 1746-1754.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.09.004] [PMID: 20840864]
[12]
Sohail, M.; Kaul, A.; Raziuddin, M.; Adak, T. Decreased glutathione-S-transferase activity: Diagnostic and protective role in Vivax malaria. Clin. Biochem., 2007, 40(5-6), 377-382.
[http://dx.doi.org/10.1016/j.clinbiochem.2007.01.005]
[13]
Antinori, S.; Galimberti, L.; Milazzo, L.; Corbellino, M. Plasmodium knowlesi: The emerging zoonotic malaria parasite. Acta Trop., 2013, 125(2), 191-201.
[http://dx.doi.org/10.1016/j.actatropica.2012.10.008] [PMID: 23088834]
[14]
Ortiz-Ruiz, A.; Postigo, M.; Gil-Casanova, S.; Cuadrado, D.; Bautista, J.M.; Rubio, J.M.; Luengo-Oroz, M.; Linares, M. Plasmodium spe-cies differentiation by non-expert on-line volunteers for remote malaria field diagnosis. Malar. J., 2018, 17(1), 54.
[http://dx.doi.org/10.1186/s12936-018-2194-8] [PMID: 29378588]
[15]
Yang, Z.; Lasker, K.; Schneidman-Duhovny, D.; Webb, B.; Huang, C.C.; Pettersen, E.F.; Goddard, T.D.; Meng, E.C.; Sali, A.; Ferrin, T.E. UCSF Chimera, MODELLER, and IMP: An integrated modeling system. J. Struct. Biol., 2012, 179(3), 269-278.
[http://dx.doi.org/10.1016/j.jsb.2011.09.006] [PMID: 21963794]
[16]
Kelley, L.A.; Mezulis, S.; Yates, C.M.; Wass, M.N.; Sternberg, M.J. Trabajo práctico No 13. Varianzas en función de variable inde-pendiente categórica. Nat. Protoc., 2016, 10(6), 845-858.
[http://dx.doi.org/10.1038/nprot.2015.053] [PMID: 25950237]
[17]
Sievers, F.; Higgins, D.G. Clustal Omega, accurate alignment of very large numbers of sequences. In: Multiple sequence alignment meth-ods; Springer, 2014; pp. 105-116.
[http://dx.doi.org/10.1007/978-1-62703-646-7_6]
[18]
Sievers, F.; Higgins, D.G. Clustal omega for making accurate alignments of many protein sequences. Protein Sci., 2018, 27(1), 135-145.
[http://dx.doi.org/10.1002/pro.3290] [PMID: 28884485]
[19]
Gascuel, O.; Steel, M. Neighbor-joining revealed. Mol. Biol. Evol., 2006, 23(11), 1997-2000.
[http://dx.doi.org/10.1093/molbev/msl072] [PMID: 16877499]
[20]
Pavlopoulos, G.A.; Soldatos, T.G.; Barbosa-Silva, A.; Schneider, R. A reference guide for tree analysis and visualization. BioData Min., 2010, 3(1), 1-16.
[http://dx.doi.org/10.1186/1756-0381-3-1] [PMID: 20175922]
[21]
Pettersen, E.F.; Goddard, T.D.; Huang, C.C.; Couch, G.S.; Greenblatt, D.M.; Meng, E.C.; Ferrin, T.E. UCSF Chimera-a visualization system for exploratory research and analysis. J. Comput. Chem., 2004, 25(13), 1605-1612.
[http://dx.doi.org/10.1002/jcc.20084] [PMID: 15264254]
[22]
Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and autodocktools4: Automat-ed docking with selective receptor flexibility. J. Comput. Chem., 2009, 30(16), 2785-2791.
[http://dx.doi.org/10.1002/jcc.21256] [PMID: 19399780]
[23]
Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2009, 31(2), 455-461.
[http://dx.doi.org/10.1002/jcc.21334]
[24]
Chusacultanachai, S.; Thiensathit, P.; Tarnchompoo, B.; Sirawaraporn, W.; Yuthavong, Y. Novel antifolate resistant mutations of Plasmo-dium falciparum dihydrofolate reductase selected in Escherichia coli. Mol. Biochem. Parasitol., 2002, 120(1), 61-72.
[http://dx.doi.org/10.1016/S0166-6851(01)00440-6] [PMID: 11849706]
[25]
Yuthavong, Y. Basis for antifolate action and resistance in malaria. Microbes Infect., 2002, 4(2), 175-182.
[http://dx.doi.org/10.1016/S1286-4579(01)01525-8] [PMID: 11880049]
[26]
Kasam, V.; Salzemann, J.; Botha, M.; Dacosta, A.; Degliesposti, G.; Isea, R.; Kim, D.; Maass, A.; Kenyon, C.; Rastelli, G.; Hofmann-Apitius, M.; Breton, V. WISDOM-II: screening against multiple targets implicated in malaria using computational grid infrastructures. Malar. J., 2009, 8(1), 88.
[http://dx.doi.org/10.1186/1475-2875-8-88] [PMID: 19409081]
[27]
Rastelli, G.; Sirawaraporn, W.; Sompornpisut, P.; Vilaivan, T.; Kamchonwongpaisan, S.; Quarrell, R.; Lowe, G.; Thebtaranonth, Y.; Yuthavong, Y. Interaction of pyrimethamine, cycloguanil, WR99210 and their analogues with Plasmodium falciparum dihydrofolate reduc-tase: Structural basis of antifolate resistance. Bioorg. Med. Chem., 2000, 8(5), 1117-1128.
[http://dx.doi.org/10.1016/S0968-0896(00)00022-5] [PMID: 10882022]
[28]
Rastelli, G.; Pacchioni, S.; Parenti, M.D. Structure of Plasmodium vivax dihydrofolate reductase determined by homology modeling and molecular dynamics refinement. Bioorg. Med. Chem. Lett., 2003, 13(19), 3257-3260.
[http://dx.doi.org/10.1016/S0960-894X(03)00676-0] [PMID: 12951104]
[29]
Kongsaeree, P.; Khongsuk, P.; Leartsakulpanich, U.; Chitnumsub, P.; Tarnchompoo, B.; Walkinshaw, M.D.; Yuthavong, Y. Crystal struc-ture of dihydrofolate reductase from Plasmodium vivax: Pyrimethamine displacement linked with mutation-induced resistance. Proc. Natl. Acad. Sci. USA, 2005, 102(37), 13046-13051.
[http://dx.doi.org/10.1073/pnas.0501747102] [PMID: 16135570]
[30]
Hiller, N.; Fritz-Wolf, K.; Deponte, M.; Wende, W.; Zimmermann, H.; Becker, K. Plasmodium falciparum glutathione S-transferase--structural and mechanistic studies on ligand binding and enzyme inhibition. Protein Sci., 2006, 15(2), 281-289.
[http://dx.doi.org/10.1110/ps.051891106] [PMID: 16385005]
[31]
Colón-Lorenzo, E.E.; Colón-López, D.D.; Vega-Rodríguez, J.; Dupin, A.; Fidock, D.A.; Baerga-Ortiz, A.; Ortiz, J.G.; Bosch, J.; Serrano, A.E. Structure-based screening of Plasmodium berghei Glutathione S-Transferase identifies CB-27 as a novel antiplasmodial compound. Front. Pharmacol., 2020, 11, 246.
[http://dx.doi.org/10.3389/fphar.2020.00246] [PMID: 32256353]
[32]
Harwaldt, P.; Rahlfs, S.; Becker, K. Glutathione S-transferase of the malarial parasite Plasmodium falciparum: Characterization of a poten-tial drug target. Biol. Chem., 2002, 383(5), 821-830.
[http://dx.doi.org/10.1515/BC.2002.086] [PMID: 12108547]
[33]
Al-Qattan, M.N.; Mordi, M.N.; Mansor, S.M. Assembly of ligands interaction models for glutathione-S-transferases from Plasmodium falciparum, human and mouse using enzyme kinetics and molecular docking. Comput. Biol. Chem., 2016, 64, 237-249.
[http://dx.doi.org/10.1016/j.compbiolchem.2016.07.007] [PMID: 27475235]
[34]
Yadav, M.K.; Swati, D. In silico study of variable surface proteins in Plasmodium species: Perspectives in drug design. Interdiscip. Sci., 2016, 8(3), 294-302.
[http://dx.doi.org/10.1007/s12539-015-0283-8] [PMID: 26253721]
[35]
Saitou, N.; Nei, M. CIWA-AR SCALE CIWA-Ar scale (Clinical Institute Withdrawal Assessment for Alcohol) assessment of alcohol abstinence syndrome. In: Mol. Biol. Evol; , 1987; 4, p. (4)406-425.
[36]
Mukinay, C.; Forlemu, N. Targeting the Plasmodium falciparum folate pathway: Molecular modelling of the affinity sulfonamide deriva-tives and isoforms of dihydrofolate reductase. Am. Chem. Soc., 2017, 2017, 254.
[37]
Adane, L.; Bharatam, P.V. Binding modes of 2,4-diaminoquinazoline and 2,4-diaminopteridine analogs to P. falciparum dihydrofolate reductase enzyme: Molecular docking studies. Indian J. Pharm. Sci., 2010, 72(3), 324-333.
[http://dx.doi.org/10.4103/0250-474X.70478] [PMID: 21188041]
[38]
Zhou, P.; Zou, J.; Tian, F.; Shang, Z. Fluorine bonding--how does it work in protein-ligand interactions? J. Chem. Inf. Model., 2009, 49(10), 2344-2355.
[http://dx.doi.org/10.1021/ci9002393] [PMID: 19788294]